Opioid Overdose and Naloxone Dosing at Insite Supervised Injection Facility in British Columbia: A Retrospective Cohort Study : Canadian Journal of Addiction

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Opioid Overdose and Naloxone Dosing at Insite Supervised Injection Facility in British Columbia: A Retrospective Cohort Study

Cho, Raymond MD1,2,3; Purssell, Roy MD, ABEM, FACMT, FRCPC1,4,5,6; Joe, Ronald MSc, MBChB7; Wang, Yueqiao Elle MSc1; O’Sullivan, Fiona BA, PhD1; Lin, Kathleen BSc1; Rowe, Adrianna BSc, MD, FRCPC1,4; Moe, Jessica MD, DABEM, MA, MSc, FRCPC1,4,6

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The Canadian Journal of Addiction 13(4):p 22-31, December 2022. | DOI: 10.1097/CXA.0000000000000162
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We aimed to understand trends in opioid overdoses, naloxone dosing, and overdose reversal from 2014 to 2017 at Insite, a community-supervised consumption site in Vancouver, British Columbia.


We performed a retrospective cohort study of patients who overdosed on opioids at Insite. We evaluated yearly trends in total overdoses, naloxone doses administered, and proportions of patients reversed (based on our definitions of “probable” and “confirmed” reversal), with particular attention to trends before and after the emergence of illicit fentanyl in 2015.


There was an increase in total overdoses at Insite from 2014–2015 (n=586) to 2016–2017 (n=2033). Overdose reversal data were limited by a large proportion of patients for whom there was not enough information to adjudicate whether reversal occurred, and therefore were marked “unspecified” [n=1537/2619 (58.7%)]. Within these limitations, fewer patients were reversed after 2015 (44.1% in 2016, 29.7% in 2017) than before (47.8% in 2014, 55.1% in 2015) (χ2=73.1, P<0.001). Despite this, naloxone doses remained unchanged between 2014–2015 and 2016–2017 {median: 0.4 mg [interquartile range (IQR): 0.4–0.8 mg] for both, P=0.21}. Insite staff administered higher doses to patients not successfully reversed [median: 0.8 mg (IQR: 0.4–0.8 mg)] compared with those reversed [median: 0.4 mg (IQR: 0.4–0.8 mg)] (P=0.021), and to patients offered transfer to hospital [median: 0.8 mg (IQR: 0.4–0.8 mg)] compared with those discharged home [median: 0.4 mg (IQR: 0.4–0.8 mg)] (Kruskal-Wallis H=288.7, P<0.001).


Overdose numbers at Insite increased and fewer patients were successfully reversed following the emergence of illicit fentanyl in 2015, but naloxone doses remained unchanged, suggesting that traditional naloxone dosing does not optimally reverse overdoses caused by fentanyl. Our study supports an alternative approach to naloxone dosing in patients with suspected ultrapotent opioid toxicity and in communities with high fentanyl prevalence.



Nous avons cherché à comprendre les tendances en matière de surdoses d’opioïdes, de dosage de naloxone et de renversement des effets de surdosage de 2014 à 2017 à Insite, un site communautaire de consommation supervisée à Vancouver, en Colombie-Britannique (C.-B.).


Nous avons réalisé une étude de cohorte rétrospective des patients ayant fait une surdose d’opioïdes à Insite. Nous avons évalué les tendances annuelles du total des surdoses, des doses de naloxone administrées et des proportions de patients qui ont renversé les effets de surdosage (selon nos définitions de “probable” et “confirmée”), en accordant une attention particulière aux tendances avant et après l'émergence du fentanyl illicite en 2015.


Il y a eu une augmentation du nombre total de surdoses à Insite entre 2014-2015 (n=586) et 2016-2017 (n=2033). Les données sur le renversement des effets de surdosage étaient limitées par une grande proportion de patients pour lesquels il n’y avait pas assez d’informations pour juger si le renversement des effets de surdosage avait eu lieu, et ont donc été marquées “ non spécifié “ (n=1537/2619 [58,7%]). Dans le cadre de ces limitations, moins de patients ont été renversé après 2015 (44,1% en 2016, 29,7% en 2017) qu’avant (47,8% en 2014, 55,1% en 2015) (χ2=73,1, P<0,001). Malgré cela, les doses de naloxone sont restées inchangées entre 2014-2015 et 2016-2017 (médiane de 0,4 mg [IQR 0,4-0,8 mg] pour les deux, P=0,21). Le personnel d’Insite a administré des doses plus élevées aux patients dont le renversement n’a pas réussi (médiane de 0,8 mg [IQR 0,4-0,8 mg]) par rapport à ceux dont le renversement a réussi (médiane de 0,4 mg [IQR 0,4-0,8 mg] (P=0. 021), et aux patients à qui l’on a proposé un transfert à l’hôpital (médiane 0,8 mg [IQR 0,4-0,8 mg]) par rapport à ceux qui ont été renvoyés chez eux (médiane 0,4 mg [IQR 0,4-0,8 mg]) (Kruskal-Wallis H=288,7, P<0,001).


Le nombre de surdoses à Insite a augmenté et moins de patients ont renversé les effets de surdosage avec succès après l'émergence du fentanyl illicite en 2015, mais les doses de naloxone sont restées inchangées, ce qui suggère que le dosage traditionnel de la naloxone ne renverse pas de manière optimale les surdoses causées par le fentanyl. Notre étude soutient une approche alternative au dosage de la naloxone chez les patients soupçonnés de toxicité aux opioïdes ultrapuissants et dans les communautés à forte prévalence de fentanyl.


The opioid epidemic is an unprecedented health crisis affecting North America with over 80,800 deaths in the United States in 2021 attributable to opioids.1 British Columbia (BC) is at the centre of this crisis and in 2016, a public health emergency was declared after epidemiologic data showed that opioid-related overdoses and death increased dramatically in mid-2015.2,3 This was fueled by the emergence of fentanyl, an ultra-potent opioid (~70 times more potent than morphine) that can cause profound respiratory depression and somnolence. Overdose deaths in which fentanyl was detected (in urine samples) grew from 25% in 2014 to 67% in 2016, and further rose to 83% in 2021.4–7

In the ever-changing landscape of the illicit drug supply, benzodiazepines like etizolam have also become increasingly prevalent contaminants in the illicit opioid supply as over 20% of opioid samples tested in Vancouver in 2021 contained benzodiazepines, compared with 9% in 2020.8 The coincident use of opioids and benzodiazepines further increases the risk of central nervous system depression.9 During the COVID-19 pandemic, overdose deaths in BC rose to historical highs with 2224 deaths in 2021 compared with 983 in 2019.7

In response to the public health emergency, the BC government created additional overdose prevention services through the newly established Ministry of Mental Health and Addictions, and the Overdose Emergency Response Centre in 2017.10 In particular, harm reduction strategies including widespread naloxone distribution and supervised consumption sites have been expanded to combat this epidemic. Naloxone is a competitive opioid antagonist that can rapidly reverse opioid toxicity and prevent anoxic brain injury.11 However, naloxone at higher doses can precipitate adverse effects and withdrawal in patients with opioid dependence.12

Unfortunately, guidelines for naloxone dosing are often outdated and based on expert opinion and experience before the emergence of illicit ultra-potent opioids in 2015.13–15 Since the emergence of illicit fentanyl, evidence suggests that higher doses of naloxone may be required to reverse toxicity caused by ultra-potent opioids.16–18 Some naloxone programs provide multiple 0.4 mg doses per kit, while others recommend higher initial doses when fentanyl is suspected.18,19 However, it is unclear whether patients treated with higher doses of naloxone have better outcomes; although these doses may result in a higher rate of adequate reversal, it is also associated with opioid withdrawal.20–22 To further complicate matters, one case series refutes this notion that higher naloxone dosing is needed in fentanyl toxicity, though their standard naloxone dose (2 mg IM) is higher than that of most guidelines.23 Given this conflicting data and the rapidly changing supply of illicit drugs, there is an urgent need to clarify an approach to naloxone dosing in suspected ultra-potent opioid toxicity.

Insite, the first community-supervised consumption site in North America, is at the front lines of the opioid epidemic in Vancouver, BC, providing an observed community location for safe injection drug use.24–26 Insite staff employs nurse practitioners, registered nurses, and licensed professional nurses who are trained to provide basic resuscitation and naloxone administration in the event of an overdose, and successfully reversed 961 opioid overdoses in 2019 alone.27 Resuscitative equipment at Insite includes oxygen via nonrebreather, bag-mask ventilation, oropharyngeal/nasopharyngeal airways, O2 saturation monitors, and IM/SC naloxone. This facility maintains records of opioid overdose events and interventions since its inception in 2003, providing a unique insight into overdose trends in communities with increasing fentanyl prevalence in the illicit drug supply.

Our primary objective was to assess the evolving trends in overdoses, naloxone dosing, and overdose reversal at Insite, with particular attention to trends following the emergence of illicit fentanyl in BC, that is, 2014–2015 versus 2016–2017. Our secondary objective was to assess the association between the dose of naloxone administered and successful reversal of opioid toxicity at Insite.


Study design

In this retrospective cohort study, we reviewed Insite records of patients who overdosed on opioids and were attended by Insite clinicians from March 2014 to November 2017.

Independent, trained data abstractors extracted data from Insite charts using standardized forms. Abstractors were trained to apply a priori definitions of naloxone dose, “confirmed reversal,” “probable reversal,” and disposition (location to which a patient was sent following an overdose event, for example, place of usual residence, hospital) when coding the data.


We included all patients documented to have received naloxone for a suspected opioid overdose at Insite (or nearby) either by an Insite clinician or bystander (n=2619). We included patients who were documented to have overdosed immediately outside of the Insite facility, as these patients would receive the same response as patients who overdosed on site (eg, trained responders with access to resuscitative equipment). We excluded patients not documented to have received naloxone.


We defined the initial dose as the first dose of naloxone given, and the cumulative dose as the sum of all naloxone doses given by any route.

Patients were defined as having an opioid overdose if a clinician suspected or confirmed opioid consumption, with associated respiratory depression and/or decreased level of consciousness requiring supplemental oxygen, bag-mask ventilation, or naloxone. Each data point represented one overdose event.

We established an a priori definition of “confirmed reversal” that required the following criteria to be met: 30 minutes after the last naloxone dose, patients had a respiratory rate >11 breaths/minute, Glasgow Coma Score >10, and oxygen saturation >91%.

Anticipating that documentation of all parameters in our “confirmed reversal” definition might be incomplete in many patients, we established an a priori definition of “probable reversal” that required the following criteria to be met: after the last naloxone dose, the patient was documented to be alert and oriented, or walking and talking (eg, conversing with staff or other participants, responding appropriately, and independently ambulatory). If there was documentation of decreased level of consciousness, unresponsiveness, obtundation, incoherent speech, inability to ambulate, or death, patients were defined as “not reversed.”

If criteria for “confirmed reversal” or “probable reversal” were not clearly documented, patient status was marked as “unspecified.”


Patients suspected of experiencing an opioid overdose were given an initial dose of naloxone, followed by further doses as necessary. Dosing was guided by the BC Centre for Disease Control clinical decision support tool, starting at 0.4 mg (or 0.4–0.8 mg in the case of muscle rigidity) and additional 0.4 mg doses at 2–3-minute intervals until patients’ respiratory rate was above 10 breaths/minute.28,29 Ultimately, clinicians applied their clinical judgement to determine when to stop giving additional doses. Resuscitative interventions were administered as determined necessary by the clinician, including oxygen administration, bag-mask ventilation, and cardiopulmonary resuscitation. The clinician also made the decision whether to recommend transfer to the hospital or discharge home.

Outcome definitions

The primary outcomes of interest were total overdose count, median naloxone dose, and proportions of overdoses successfully reversed each year between 2014 and 2017. The secondary outcomes were reversal status using both “confirmed reversal” and “probable reversal” definitions, and disposition following naloxone administration. Patient information upon leaving Insite was unavailable.

Data analysis

We analyzed the annual trends in total overdoses seen at Insite, naloxone dose, and proportion of successful reversal from 2014 to 2017. We reported naloxone doses administered as medians with interquartile range (IQR). We compared the proportion of successful reversal between 2014–2015 and 2016–2017 using χ2 tests. In addition, we performed a priori subgroup analyses to determine whether naloxone doses differed based on study year, reversal status, and disposition. We stratified naloxone doses by reversal and disposition status, and compared median doses within these categories using nonparametric Kruskal-Wallis H and pairwise tests.

We performed sensitivity analyses assuming (1) a “best case scenario,” that all overdoses marked unspecified were reversed, and (2) a “worst case scenario,” that all overdoses marked unspecified were not reversed. We chose a “best case scenario” that would provide the most optimistic estimate of naloxone effectiveness. Conversely, our “worst case scenario” sensitivity analysis would provide the most cautious estimate of naloxone effectiveness, allowing a measured interpretation of our results. We planned these sensitivity analyses to mitigate the high degree of unspecified outcomes we anticipated, given the strict reversal definitions we applied.

We also assessed interrater reliability by reviewing a random sample of 150 charts. An independent assessor checked the following variables to assess for accuracy in data extraction and coding: inclusion/exclusion criteria, cumulative naloxone dose, time of naloxone administration, “confirmed reversal” status, “probable reversal” status, and disposition. The overall κ score was 0.895, indicating good interrater reliability among coders for the variables assessed.

Statistical analysis was performed with R (R Foundation for Statistical Computing, Vienna, Austria, version 3.6.1, 2019).


We identified 2619 patients who were managed by Insite clinicians for a suspected opioid overdose from March 2014 to November 2017 (Table 1). The majority of patients were male (79.3%), and the most common age group was 30–39 years (27.5%). In addition, most patients (75.2%) were found to have overdosed on-site. Twenty-eight percent of patients were suspected to be apneic on initial assessment and 29.9% unresponsive to stimulation. 93.7% of patients were given supplemental oxygen and other resuscitative interventions. No patients died during their Insite visit.

Table 1 - Characteristics of Patients and Overdose Events Attended by Insite Clinicians
Characteristics Frequency Percentage (%)
Total overdose events 2619 100.0
 2014 312 11.9
 2015 274 10.5
 2016 954 36.4
 2017 1079 41.2
Patient characteristics
  Male 2078 79.3
  Female 449 17.1
  Unspecified 92 3.5
 Age (yr)
  10–19 36 1.4
  20–29 514 19.6
  30–39 720 27.5
  40–49 545 20.8
  50–59 450 17.2
  60–69 249 9.5
  70+ 105 4.0
Overdose event characteristics
 Location of overdose
  At Insite 1969 75.2
  Off-site 529 20.2
  Unspecified 121 4.6
 Suspected respiratory arrest
  Yes 743 28.4
  No 419 16.0
  Unspecified 1457 55.6
 Completely unresponsive to stimulation
  Yes 784 29.9
  No 325 12.4
  Unspecified 1510 57.7
 Other illicit substances recorded
  Yes 316 12.1
  No (patient denies) 355 13.6
  Unspecified 1948 74.4
 Oxygen supplementation provided
  Yes 2454 93.7
  No 84 3.2
  Unspecified 81 3.1

We observed an increase in the numbers of documented opioid overdoses at Insite, and decreased rates of successful reversal in 2016–2017 compared with 2014–2015 (Fig. 1). Insite staff responded to 2033 opioid overdoses in 2016–2017 compared with 586 in 2014–2015. Based on the “confirmed reversal” definition, fewer patients were successfully reversed after 2015 (25.8% in 2016, 22.9% in 2017) than during and before 2015 (31.4% in 2014, 28.8% in 2015, χ2=10.4, P<0.001) (Fig. 1A). Similarly, we observed decreased proportions of reversal after 2015 using our “probable reversal” definition (47.8% in 2014, 55.1% in 2015, 44.1% in 2016, and 29.7% in 2017, χ2=73.1, P<0.001) (Fig. 1B).

Figure 1:
Reversal status by visit year based on: (A) “confirmed reversal” criteria. B, “Probable reversal” criteria.

We found that the initial naloxone dose (0.4 mg) remained unchanged throughout the study period (2014–2017) and found no significant difference in initial dose among all subgroups based on reversal status and disposition (probable reversal: Kruskal-Wallis H=2.2, P=0.33; confirmed reversal: Kruskal-Wallis H=4.0, P=0.14; disposition: Kruskal-Wallis H=4.5, P=0.20). Similarly, we found no significant difference in the cumulative naloxone doses between patients treated in 2014–2015 compared with those in 2016–2017 [median: 0.4 mg (IQR: 0.4–0.8 mg) for both, Kruskal-Wallis H=1.7, P=0.21].

In 2014–2015, 130 (73.9%) patients were given 1 dose, 39 (22.2%) were given 2 doses, and 7 (4.0%) were given 3 doses of naloxone among those who were “confirmed” reversed. Similarly, in 2016–2017, 366 (74.2%) patients were given one dose of naloxone, 112 (22.7%) were given 2 doses, and 15 (3.0%) were given 3 doses among those “confirmed” reversed. In contrast, among patients not reversed in 2014–2015, 8 (42.1%) received 1 dose, 9 (47.4%) received 2 doses, and 2 (10.5%) received 3 doses of naloxone. Among those not reversed in 2016–2017, 18 (36.7%) received 1 dose, 24 (49.0%) received 2 doses, and 7 (14.3%) received 3 doses of naloxone.

We determined that cumulative naloxone doses were higher in patients not successfully reversed than those reversed based on both the “confirmed” [unsuccessful: median: 0.8 mg (IQR: 0.4–0.8 mg); successful: median: 0.4 mg (IQR 0.4–0.8 mg), Kruskal-Wallis H=490.0, P<0.001] and “probable” reversal definitions (unsuccessful: median: 0.8 mg (IQR: 0.4–0.8 mg); successful: median: 0.4 mg (IQR: 0.4–0.8 mg), Kruskal-Wallis H=246.4, P=0.021] (Table 2, Fig. 2A). We also observed that doses were higher in patients transferred or declined transfer to hospital [median: 0.8 mg (IQR: 0.4–0.8 mg)], compared with patients discharged home [median: 0.4 mg (IQR: 0.4–0.8 mg), Kruskal-Wallis H=288.7, P<0.001] (Table 2, Fig. 2B).

Table 2 - Cumulative Naloxone Dose Stratified by Reversal and Disposition Status Following Insite Visit
N Median dose (mg) IQR (mg)
Reversal Status
 “Confirmed reversal”
  No 68 0.8 0.4–0.8
  Yes 670 0.4 0.4–0.8
  Unspecified 1881 0.4 0.4–0.8
 “Probable reversal”
  No 40 0.8 0.4–0.8
  Yes 1042 0.4 0.4–0.8
  Unspecified 1537 0.4 0.4–0.8
Disposition status
 Hospital 566 0.8 0.4–0.8
 Refused hospital 585 0.8 0.4–0.8
 Home 772 0.4 0.4–0.8
 Unspecified 696 0.4 0.4–0.8

Figure 2:
Cumulative naloxone dose stratified by (A) reversal status. B, Disposition following Insite visit.

In our sensitivity analyses, if we assumed a “best case scenario” wherein all unspecified cases were reversed, cumulative naloxone doses were higher in patients who were not reversed than those reversed using both confirmed [unsuccessful: median: 0.8 mg (IQR: 0.4–0.8 mg); successful: median: 0.4 mg (IQR: 0.4–0.8 mg), Kruskal-Wallis H=16.5, P<0.001] and probable definitions (unsuccessful: median: 0.8 mg (IQR: 0.8–1.0 mg); successful: median: 0.4 mg (IQR: 0.4–0.8 mg), P=0.007]. On the contrary, if we assumed a “worst case scenario” wherein all unspecified cases were not reversed, cumulative doses administered to those who were and were not reversed were significantly different, though the direction of the difference was not clear [confirmed reversal—unsuccessful: median: 0.4 mg (IQR: 0.4–0.8 mg); successful: median: 0.4 mg (IQR: 0.4–0.8 mg), Kruskal-Wallis H=53.5, P<0.001. Probable reversal—unsuccessful: median: 0.4 mg (IQR: 0.4–0.8 mg); successful: median: 0.4 mg (IQR: 0.4–0.8 mg), Kruskal-Wallis H=5.4, P=0.02].


Interpretation of findings

We aimed to understand the trends in overdoses, naloxone dosing, and reversal status over time at Insite, a community-supervised consumption site in Vancouver, BC. Insite provided an unparalleled opportunity to explore longitudinal trends in overdose incidence and management, in a setting and population that is challenging to study. Our data showed that the number of overdoses increased markedly after December 31, 2015, following the emergence of fentanyl in BC’s illicit drug supply. Fewer patients were defined as “successfully reversed” in 2014–2015 than in 2016–2017, while cumulative naloxone doses administered remained unchanged. We also showed that clinicians used higher naloxone doses in patients not successfully reversed than reversed, and in those offered transport to the hospital compared with those discharged home, both likely proxies of opioid overdose severity.

The increased number of overdoses at Insite over time likely reflects increasing overdose severity (ie, apnea and/or complete unresponsiveness) with exposure to illicit fentanyl. BC public health data showed that illicit drug deaths in which fentanyl was detected increased from 29% in 2015 to 67% in 2016.4 In addition, the declining proportion of successful opioid toxicity reversal post-2015, coupled with unchanged naloxone dosing at Insite provides further evidence that fentanyl overdoses may be less readily reversible at usual naloxone doses than overdoses from other opioids. Previous studies have also shown that opioid overdoses are increasingly challenging to manage in the fentanyl era potentially due to fentanyl-induced chest rigidity that impedes effective ventilations.30,31 Therefore, our data suggests that an alternative approach to naloxone dosing may be required in community settings with high fentanyl prevalence.

Our finding that higher naloxone doses, both cumulative dose and number of doses given, were administered to patients not successfully reversed reflects that nonreversal is an indicator of more severe overdose. Similarly, the association between higher doses and being offered transfer to the hospital indicates that disposition is another marker of overdose severity. Patients who were not reversed or were offered transport to the hospital likely experienced a more severe overdose, which resulted in higher naloxone doses, and a greater number of doses administered, and reflects confounding by indication. Our finding that greater proportions of patients who were not reversed received multiple doses of naloxone in 2016–2017 than in 2014–2015 suggests that the severity of overdoses increased in the later years of our study when the prevalence of fentanyl increased in the illicit drug supply.

Comparison to previous studies

A recent study showed that fentanyl was increasingly detected by patients using drug testing services at Insite post-2015, which confirms our suspicion that growing fentanyl prevalence underlies the increase in overdose numbers in our study population at Insite.32 Additionally, a systematic review of naloxone dosing in the era of ultra-potent opioids primarily in emergency departments, showed that fewer patients with fentanyl toxicity responded to naloxone compared to overdoses caused by other opioids, which supports our findings in the community setting at Insite.33 Similar to our secondary results, this review also found that higher doses of naloxone were administered in patients who were not successfully reversed and in those who were treated in the emergency department compared with community settings.

Strengths and limitations

Our study analyzed overdose and naloxone data in a community population that is challenging to research due to a lack of data and trained providers. Insite, a supervised consumption site, provides an unprecedented opportunity to understand trends in overdose, naloxone dosing, and overdose reversal in a community setting, and provides higher quality longitudinal data (2014–2017) than previously available.

Despite access to this data, our study was limited by inconsistent documentation. Due to incomplete documentation, our abstractors determined that a high proportion of patient reversal statuses were “unspecified” using the “confirmed reversal” definition [n=1881/2619 (71.8%)]. We attempted to minimize this limitation by including a “probable reversal” definition, but a large proportion of overdose outcomes were still marked as “unspecified” due to incomplete documentation [n=1537/2619 (58.7%)]. In our assessment of reversal trends over time, we primarily used the proportion of patients who were marked as “reversed,” though we also did assess the trends of patients marked “not reversed.” Unfortunately, there was no clear trend in this population, likely as a result of stringent criteria (ie, postnaloxone respiratory rate, GCS, and oxygen saturation that did not meet criteria for reversal), which was not available in many participant charts, as well as our hypothesis that Insite clinicians were less likely to have documented completely in patients who were not reversed as they would be busy attending to clinical care. For these reasons, we focused our discussion on reversal trends on patients who were marked “reversed” than those “not reversed” as we believe that this is a more reliable measure.

To mitigate the impact of incomplete documentation, we completed sensitivity analyses. In a “best case” scenario, we continued to find that patients who were not reversed received higher naloxone doses. However, in a “worst case” scenario, patients who were reversed and not reversed received similar naloxone doses. Our differential findings on sensitivity analyses do indicate limitations of our data, and emphasize that our analyses are exploratory rather than definitive. Similarly, the lack of clear documentation made it challenging to ascertain important variables including patient co-morbidities/risk factors, which could influence successful overdose reversal and the dose of naloxone required. Despite data limitations, our analysis provides important observations about opioid overdose reversal in community settings that provide an important basis for future, definitive analyses in more rigorous trials.

Based on our clinical and experiential knowledge of Insite procedures, we expect documentation of naloxone doses to be more accurate than information requiring clinical assessment of patients. Nonetheless, our analyses are reliant on dosing information we abstracted from charts and potential inaccuracies are a limitation. In addition, patients with overdoses who were transported to the hospital may have received additional naloxone and potentially demonstrated further clinical response upon leaving Insite, but this data was unavailable. This may have led to inaccurate assessments of total naloxone doses administered, and misclassification of reversal status if treatment and clinical response progressed.

Finally, our data is current only until 2017, due to delays in data acquisition and the labour-intensive process of data extraction. The constantly changing landscape of the illicit drug supply (eg, fluctuating levels of ultra-potent opioids) make it challenging to establish recommendations for naloxone administration specifically tailored to current realities.34 In particular, benzodiazepines like etizolam have become increasingly prevalent contaminants in the illicit opioid supply in BC.8 Furthermore, we do not have information on the composition and contaminants of the illicit opioids to which patients were exposed, and therefore are unable to contextualize our data on naloxone effectiveness based on the agent of overdose. Despite our lack of data beyond 2017 and information on drug composition, our study provides the only longitudinal published report on naloxone administration at an overdose prevention site before and after fentanyl emergence in BC, and therefore contains information crucial to share with other jurisdictions that are experiencing similar evolutions in their illicit drug supply.

Clinical and research implications

Our data showed that the proportions of overdoses that were successfully reversed at Insite decreased over time after the emergence of illicit fentanyl in BC, suggesting that our usual approach to naloxone dosing in communities with high fentanyl prevalence is no longer optimal. Although our data do not clarify the preferred approach, alternatives may include more frequent titration of naloxone doses and/or a need for responders to anticipate the need for higher cumulative total doses. Higher naloxone doses may lead to opioid withdrawal in patients with opioid dependence, which is not only extremely unpleasant but also dangerous, as it may lead patients to use opioids again to self-treat withdrawal symptoms.11 Our work does, however, reflect the importance of ensuring that adequate doses of naloxone (eg, 3 or more vials of 0.4 mg provided in take-home naloxone kits) are available in communities with high fentanyl prevalence to allow rapid titration to clinical response.35

There is an urgent need to clarify best clinical practices for naloxone dosing in patients suspected of a severe, fentanyl overdose in these communities. Although our data did not allow an evaluation of dosing schedules, further research should specifically assess the effectiveness and safety of more frequent redosing of naloxone than current guidelines suggest (every 2–3 minutes).28,29 This is especially important in the context of the COVID-19 pandemic, in which reducing time-to-reversal is critical to minimize aerosolizing procedures including assisted respirations, chest compressions, and airway procedures.36 These future studies should focus on obtaining high-quality, prospective data using standardized outcome definitions, to compare the effectiveness of different naloxone dosing strategies in reversing opioid toxicity and avoiding adverse events, particularly in community settings like Insite.


Our study showed that opioid overdoses increased dramatically, and fewer patients were successfully reversed, while naloxone doses remained unchanged at Insite after the emergence of illicit fentanyl in 2015. Therefore, our analysis suggests the need for an alternative approach to naloxone dosing, such as more frequent titration and/or higher cumulative totals, in communities with high fentanyl prevalence.


The authors thank Mina Karimi, Christine Gillespie, and Mina Park, the managers of Insite for their instrumental role in the conception of this study. They also thank Andrew Chang, Emily Lostchuck, Connor McSweeney, Paul Clerc, and Victoria McCann for their roles in data abstraction.


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Naloxone; Fentanyl; Opioid-Related Disorders; Opiate Overdose; supervised consumption site; Naloxone; Fentanyl; Troubles liés aux opioïdes; Surdose d’opiacés; Site de consommation supervisée

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